Epitopes described in "Quantitative and functional analysis of PDC-E2-specific autoreactive cytotoxic T lymphocytes in primary biliary cirrhosis."

Article Authors:Hiroto Kita; Shuji Matsumura; Xiao-Song He; Aftab A Ansari; Zhe-Xiong Lian; Judy Van de Water; Ross L Coppel; Marshall M Kaplan; M Eric Gershwin
Article Title:Quantitative and functional analysis of PDC-E2-specific autoreactive cytotoxic T lymphocytes in primary biliary cirrhosis.
Reference Detail
Reference ID:1017211
Abstract:While the pathologic mechanisms responsible for organ-specific tissue damage in primary biliary cirrhosis (PBC) remain an enigma, it has been suggested that the pathology is mediated by autoreactive T cells infiltrating the intrahepatic bile ducts. Previously, we have documented that there is 100-fold enrichment in the frequency of CD4(+) autoreactive T cells in the liver that are specific for peptides encoded by the E2 components of the pyruvate dehydrogenase complexes (PDC-E2). We have also recently characterized the first MHC class I-restricted epitope for PDC-E2, namely amino acid 159-167, a region very similar to the epitope recognized by MHC class II-restricted CD4(+) cells and by autoantibodies. The effector functions of these PDC-E2(159-167)-specific CD8(+) cytotoxic T lymphocytes (CTLs) are not well understood. We have taken advantage of tetramer technology and report herein that there is tenfold increase in the frequency of PDC-E2(159-167)-specific CTLs in the liver as compared with the blood in PBC. In addition, the precursor frequency of the CTLs in blood was significantly higher in early-stage PBC. Of interest was the fact that, upon stimulation with the peptide, the response of PDC-E2(159-167) tetramer-positive cells is heterogeneous with respect to IFN-gamma synthesis. These data, we believe for the first time, document the enrichment of autoantigen-specific CD8(+) T cells in the PBC liver, suggesting that CD8(+) T cells play a significant role in the immunopathogenesis of PBC.
Affiliations:Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, California 95616, USA.
Reference Type:Literature
PubMed ID:11994412
Journal:J Clin Invest
Journal Volume:109
Article Pages:1231-40
Journal ISSN:0021-9738
Article Chemical List:Autoantigens;Epitopes;HLA-A Antigens;HLA-A*02:01 antigen;HLA-A2 Antigen;Pyruvate Dehydrogenase Complex;Interferon-gamma;Dihydrolipoyllysine-Residue Acetyltransferase
Article MeSH List:Autoantigens(immunology); Cells, Cultured; Dihydrolipoyllysine-Residue Acetyltransferase; Epitopes(immunology); Flow Cytometry; HLA-A Antigens(immunology); HLA-A2 Antigen; Humans; Interferon-gamma(biosynthesis); Liver(immunology); Liver Cirrhosis, Biliary(immunology); Pyruvate Dehydrogenase Complex(immunology); T-Lymphocytes, Cytotoxic(immunology)
Curation Last Updated:2016-05-06 20:01:27